image: Figure | Working principle of HyFMRI and in vivo experimental results. a, schematic drawing of the hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI) platform for measuring neuronal and astrocytic activity registered to concurrently recorded brain-wide hemodynamic responses. The platform incorporates a fiberscope-based optical (multichannel FL and optical intrinsic signal) imaging system and a custom surface radiofrequency (RF) coil into the bore of a preclinical MRI scanner. Custom 3D-printed components were designed to bridge the two modalities and provide animal support during the experiment. b-d, astrocytic, neuronal and hemodynamic brain activation patterns, respectively, evoked by external electrical forepaw stimulation from a representative mouse.
Credit: Zhenyue Chen et al.
A critical gap currently exists in systematic understanding and experimental validation of the role of astrocytes in neurovascular coupling and their functional links with other brain cells. Despite a broad selection of functional neuroimaging tools for multi-scale brain interrogations, no methodology currently exists that can discern responses from neural and glial cells while simultaneously mapping the associated hemodynamic activity on a large scale.
In a new paper published in Light: Science & Applications, a team of scientists, led by Professor Daniel Razansky from ETH Zurich and University of Zurich developed a hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI) platform for measuring neuronal and astrocytic activity registered to concurrently recorded brain-wide hemodynamic responses. The platform features a fiberscope-based imaging system for multichannel fluorescence and optical intrinsic signal recordings and a custom surface radiofrequency coil, which are incorporated into the bore of a preclinical magnetic resonance imaging (MRI) scanner.
Genetically encoded calcium indicators (GECIs) have profoundly transformed neuroscience by enabling the visualization and quantification of calcium dynamics within neurons and other cell types. Despite its powerful multiparametric imaging capabilities, functional MRI is inherently limited when it comes to sensing molecular information. In the following the scientists summarize their motivation for this work:
“Combining calcium imaging with fMRI can allow for the direct measurement of local neural activity and the associated hemodynamic responses and this is of paramount importance in functional neuroscience. However, integration between concurrent fluorescence calcium recordings with fMRI is not straightforward due to electromagnetic interference inside the MRI scanner. To this end, optical recordings and fMRI from the same subject have mainly been performed sequentially or using invasive fiber photometry approaches, making it challenging to link measurements across spatial and temporal scales and modalities. We present a new approach termed HyFMRI for hybridizing multiplexed optical and MRI recordings by incorporating a fiberscope-based optical module and a custom surface radiofrequency coil into the bore of a preclinical MRI scanner.”
“HyFMRI holds several significant advantages over conventional photometry-based approaches and stand-alone widefield fluorescence imaging. First, it can measure cortex-wide neural activity simultaneously with fMRI, making it particularly suitable for brain function studies at the level of large networks or circuits. Second, HyFMRI is minimally invasive and easy to implement. This avoids significant drawbacks of photometry-based approaches. Last but not least, despite being limited by light scattering in the brain tissue, HyFMRI achieves a reasonable balance between spatial resolution and whole-cortical coverage. Given its compact design, HyFMRI platform holds potential for future integration with additional modalities, such as optoacoustic imaging, optogenetics, or transcranial ultrasound stimulation to answer more sophisticated questions.” they added.
“The integration of these two advanced imaging modalities, fluorescence and MRI, addresses a long-standing challenge in neuroscience—capturing both cellular-level activity and whole-brain hemodynamics in the same experiment. This achievement could help accelerate research into brain diseases, enabling the development of more targeted therapies and deepening our understanding of brain function.” the scientists forecast.
Article Title
Non-invasive large-scale imaging of concurrent neuronal, astrocytic, and hemodynamic activity with hybrid multiplexed fluorescence and magnetic resonance imaging (HyFMRI)